In vitro cell culture systems have great potential as biological models of an bioassay systems for oncogenic and mutagenic activity of environmental chemicals and other agents to which man may be exposed. Presently, in vitro models of chemo-oncogenesis utilize rodent cells exclusively, and of these, the systems most useful for bioassay are deficient in drug metabolizing ability. We propose to overcome both these difficulties by addition of human liver cells to these systems, thus providing an active drug metabolizing element in vitro closely approximating the species-specificity of in vivo human drug metabolism. Similarly, in vitro models of chemo-mutagenesis are based upon established lines of rodent cells, for which the biochemical responses to chemical injury of the genetic material have been demonstrated to be qualitatively different from man. Fortunately, the recent development of a human cell line, mutable by chemical agents, promises to obviate this important difficulty in extrapolating in vitro observations to the human condition. We propose to apply this new mutable human cell line in combination with human liver cells to create an "all-human" assay system for chemo-mutagenic activity. Thus, both drug metabolizing and target elements of the in vitro model will, for the first time, be of human derivation. The necessary characterization of these new systems will be performed by studying the activity of a series of ten in vivo oncogens and mutagens which require a broad spectrum of metabolic steps for expression of chemicobiological activity. Quantitative studies permitting comparison among test compounds and assay systems represent the basic fabric of our experimental design through which we mean to discover the strengths and deficiences of these in vitro models of chemically induced human disease.